Microenvironment Design for Stem Cell Fate Determination - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 242

Fig. 5 Morphology of porous alginate scaffold incorporating PLGA microspheres capable of
controlling the release of basic fibroblast growth factor. SEM picture of (a) microspheres, (b-c)
the alginate composite scaffold (reprinted by permission from [ 80 ])
molecule may be delivered in a sustained release profile from matrix-embedded
micro-particles, be covalently immobilized to the matrix, or be presented via
affinity interactions.
Controlled Release Delivery of Signaling Molecules From Micro-Particles
In an attempt to design a dynamic cell microenvironment, where the regulatory
signals often vary in space and time, microparticles for controlled delivery of
signaling molecules have been developed and incorporated into the scaffolds
(Fig. 5 )[ 80 ]. In this way, molecule release is typically controlled through diffu-
sion, particle degradation, or their combinations, leading to a wide range of factor
delivery profiles. Moreover, the wide versatility of these systems is associated with
other variables that can be modeled to obtain an optimal system for a specific
application, such as particle composition, size and shape.
The incorporation of microparticles into scaffolds has been widely used to
control stem cell fate decision. For example, gelatin microparticles loaded with
TGFb1 were co-encapsulated with rabbit MSCs in an injectable biodegradable
hydrogel composites of oligo(poly(ethylene glycol) fumarate). The localized
delivery of TGFb1 resulted in an efficient chondrogenic differentiation, revealed
by the increase in glycosaminoglycan content per DNA and the upregulation of
chondrocyte-specific gene expression of type II collagen and aggrecan [ 152 ].
One recent study involved the combined application of immobilized RGD
dextran-based hydrogel and microencapsulated vascular endothelial growth factor
(VEGF) to induce vascular differentiation of hESCs [ 153 ]. HESCs within the
bioactive hydrogels expressed higher levels of vascular markers, compared to
spontaneously differentiated embryoid bodies (EBs). Carpenedo et al. [ 154 ]
showed that using polymer microspheres for the delivery of morphogenic factors
directly within EB microenvironments in a spatio-temporally controlled manner
yielded homogeneous, synchronous and organized ESC differentiation. Degrad-
able PLGA microspheres releasing retinoic acid were incorporated directly within