10. Alginate foams
Macroporous scaffolds as foams or sponges for tissue engineering
applications may provide improved cell invasion and improved mass
transport of nutrients, oxygen and waste removal. Porous scaffolds may
easier facilitate formation of multicellular aggregates inside the pores of the
foam due to the predefined open space and possible 3D cell-cell interaction.
The most common technique for production of alginate foams is freeze
drying. lonically gelled alginate foams with interconnected pores can be
made with controllable pore size, pore wall thickness and elasticity by
changing formulation and processing parameters.’° 2In addition to or in
combination with freeze-drying are also porous structures prepared using
porogen salts and passage of gas through covalently cross-linked gels,’° 3in
situ gas formation in alginate solution followed by ionic c1ross0-link4ing or
covalent dissolution of gelatin beads embedded in alginate
hydrogels by temperature i1nc0rea6se and precipitation of alginate with
cationic polymers such as chitosan)° 7’108
Foams may be implanted with or without cells. When implanting cellfree
scaffolds, they can be infiltrated by host cells and used as a temporary
extracellular matrix guiding formation of new tissue for example for repair
of soft tissue defects,’° 4bone regeneration’° 8and formation of new blood
v8ess2els. Cell-free scaffolds with controllable degradation profiles loaded
with signalling molecules such as drugs or growth factors can provide
sustained delivery to the site of interest. 82 ’ I07 Cells can also be seeded into
foams and cultured for a short time in vitro and then be implanted for
example as heart patches for cardiac tissue regeneration 78or lymphoid-like
cell constructs with immunosuppressive properties.’° 93D cell culture in
vitro may be important for drug discovery including efficiency modulation,
elucidating drug metabolism and toxicity profiles using, for example, cell
laden alginate constructs as an artificial Examples of other in vitro
uses include formation of embryonic bodies from human embryonic stem
cells” and controlled differentiation of MSCs to chondrocytes by presentation of inductive cues relevant for cartilage tissue engineering
applications.’12
The use of 3D cell culture is increasing as growth in a 3D matrix better
can approximate cell-ECM and cell-cell interactions as found in tissues,
organs and tumours compared to traditional 2D cell culture methods. It
has also been demonstrated using breast cancer cell lines cultured in 3D
and 2D that cell signalling pathways, gene expression and cell morphology
are different.’’3’114 Studies with a murine mesenchymal stem-cell line
showed that different integrins acted as RGD receptors depending on
whether the cells were cultured on or within alginate hydrogels of same the
elasticity and RGD density.79 3D cell culture is currently performed by
several groups using a reconstituted basement membrane from murine
Engelbreth-Holm-Swarm tumours. As this animal derived material will
have inherent variability within the ECM molecules and will likely not be
relevant for in vivo use, alginate cell culture systems such as alginate foams
may be an interesting alternative.”