Biomaterials for Cell-Based Therapeutic Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 245

Therefore, this chapter will discuss strategies for the biomaterial design of cell-
based revascularization therapies, including control of material properties and
microstructure and processes for loading cells into the materials. We will spe-
cifically focus on describing the design of porous polymer scaffolds, fibrous
scaffolds, and hydrogels. In parallel, the influence of these biomaterial properties
on improving cell viability, angiogenic function, and subsequent revascularization,
both in vitro and in vivo, will be reviewed.
2 Biomaterial Design
2.1 Porous Scaffold
Cell-laden porous scaffolds are increasingly used to enhance vascularization
throughout implants because of their potential to facilitate the migration of blood
vessel-forming cells into the scaffold and further stimulate endothelial lumen
formation within the micro-sized pores. It is common to first assemble the scaffold
with interconnected micropores and subsequently plate cells. The cells used in
these scaffolds include cells that secrete angiogenesis factors to neighboring tis-
sues, those that possess a potential to differentiate to endothelial cells, or both cells
types.
These porous scaffolds are commonly prepared with biodegradable polymers,
such as poly(lactide-co-glycolic acid) (PLGA), poly(e-caprolactone), polyanhy-
drides, cross-linked collagen and glycosaminoglycan, and their derivatives [ 7 ].
Mechanical properties and degradation rates of these polymeric matrices are
controlled by the fraction of hydrolyzable units, molecular weights, and hydro-
philicity of the polymer. These polymers are co-polymerized with other polymeric
units, such as poly(ethylene glycol) and polysaccharides, to further control
material properties and interactions with host immune systems [ 7 ]. Alternatively,
these polymers are physically mixed or chemically conjugated with cell adhesion
peptides or proteins in order to control cellular adhesion to polymeric matrices.
It is common to incorporate the interconnected micropores into the polymeric
matrices via porogen leaching, gas foaming, freeze drying, and phase separation
(Fig. 2 )[ 7 ]. Recently, diameters of micropores are controlled in a more sophis-
ticated manner by incorporating microparticles with uniform diameters into the
polymeric matrices and leaching them out using solvents (Fig. 2 )[ 7 ]. Therefore,
the biocompatibility of the porous matrices tends to significantly depend on types
of porogen and microparticles used because they determine the solvents that
should be used to create the interconnected pores [ 8 ]. In this regard, the gas
foaming or freeze drying process may exhibit advantages with minimal concerns
of cytoxic residues in the porous matrix, but these methods still present limited
controllability of pore size [ 9 ].