Biomedical Engineering Reference
In-Depth Information
Infiltrating a fiber-based scaffold with a hydrogel is a popular form of composite scaffold.
However, the cell-material interactions are critically important to the overall success of the construct.
In previous studies, chondrocytes encapsulated in alginate were combined with either PLGA or
demineralized bone matrix (DBM) before implantation into mice for eight weeks [
373
].The PLGA-
alginate composite produced collagen type II, a positive indicator of cartilage formation. The DBM-
alginate composite, however, did not produce collagen type II. The cell response could be modified
by substituting other hydrogels or including growth factors, but the base scaffold materials will still
play a major role in the type of matrix deposited in the construct.
Another approach to composite materials is to reinforce solid scaffolds with fibers oriented in
specific directions. By embedding fibers in a scaffold, the mechanical properties can be modified to
improve strength in preferred directions. This is particularly important for anisotropic tissues such
as articular cartilage. Fiber reinforced scaffolds can be fabricated using any combination of materials.
Past studies have investigated PGA fiber-reinforced PLGA and found that the compressive modulus
and yield strength improved by up to 20% [
374
]. Carbon fibers, while seemingly unadvisable for joint
implantation, have been used with satisfactory clinical results for filling defects
in vivo
[
375
,
376
].
Success rates of 70-80% were achieved based on qualitative measures of pain several years after
implantation.
Composite scaffolds that incorporate several different types of materials can help replicate
the complex structure necessary for providing functional properties appropriate to load-bearing tis-
sues [
377
]. One approach that shows promise is to fabricate three-dimensional structures that exhibit
mechanical properties similar to articular cartilage immediately after implantation. Woven scaffolds,
such as alginate-filled PCL meshes [
292
], can provide both mechanical strength, anisotropy, and a
beneficial growth environment.
3.3.4 SCAFFOLDLESS
Though scaffolds can serve as an additional tool in controlling tissue development (e.g., with the
slow release of growth factors or pre-patterned to influence organization), they also bring with
them issues such as degradation toxicity, stress shielding, and cell signaling hindrance. Techniques
have also been developed using chondrocytes to create scaffoldless constructs [
312
,
378
-
381
]. Via
centrifugation, chondrocyte pellets can be formed and grown in culture. With gentle or no fluid
movement (e.g., rotational culture [
382
] or low density seeding on agarose [
383
]), larger aggregates
have also been formed. It was proposed that the formation of numerous aggregates may serve as a
3-D culture methodology for chondrocyte expansion [
382
] while aggregates of limb bud cells have
been used to examine parallels in development [
383
].
Emerging from the developmental studies, scaffoldless culture has been proposed as a method
to engineer functional articular cartilage of sufficient dimensions. For instance, a self-assembly
method has been developed based on the differential adhesion hypothesis to produce robust car-
tilage constructs that contained two thirds more GAG than native tissue, and collagen levels that
reached one third the amount of native tissue. Neocartilage thus formed contain collagen type II and
