Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 304

Fig. 14.5 Microparticle and scaffold fabrication process. ( a ) Microspheres were made from a
polymer stream (20%w/v PLGA containing growth factors) and annular carrier stream (0.5%w/v
PVA in ddH 2 O) with an ultrasonic transducer; ( b ) Programmable syringe pumps created a gradient
in microsphere types (adapted, with permission, from [ 108 ])

exhibited osteogenic and chondrogenic differentiation along the concentration
gradients in the single gradient of BMP-2 and reverse gradient of BMP-2/IGF-1, but
not the IGF-1 gradient system. They also pointed out that the carrier systems also have
a significant role in the delivery and release kinetics of growth factors that might
influence gene expression.
Our group followed the approach of making continuous gradients of bioactive
signals using a microsphere-based technology [ 105 ]. Microspheres allowed encap-
sulation of bioactive signals and the gradient technology enabled localization of
signals at specific sites within the scaffold. A precision particle fabrication process
was used to make monodisperse microparticles and programmable syringe pumps
were used to create the gradient profiles. Continuous gradient osteochondral
scaffolds were fabricated using PLGA microspheres encapsulated with a chondro-
genic signal TGF- 1 or osteogenic signal BMP-2. A schematic representation of

fabrication process is shown in Fig. 14.5 . These microspheres were collected in a
mold and sintered to form a 3D osteochondral scaffold with continuous opposing
gradients of chondrogenic and osteogenic signals. Microspheres enabled control
over growth factor concentrations and release kinetics and the sintering conditions
and the microsphere size enabled control over the pore sizes of the scaffold. The
microspheres together with our gradient technology enabled spatial localization of
bioactive signals, and this approach was useful for fabricating an integrated scaffold
that favored simultaneous triggering of osteochondral induction. The continuous
gradient scaffolds outperformed the biphasic constructs in GAG and calcium
content when seeded with human umbilical cord mesenchymal stromal cells over
a 6-week period [ 45 ]. We also explored the possibility of making continuous
stiffness gradient scaffolds by orienting the PLGA microspheres and CaCO 3
incorporated PLGA microspheres using this technology [ 106 ].
Scaffolds with a continuous gradient in bioactive signals and material composition
might guide tissue-specific differentiation of progenitor cells at

b

the interface.