Biomedical Engineering Reference
In-Depth Information
38 CHAPTER 3.
IN VITRO
TISSUE ENGINEERING
regeneration are found with bone therapy and bone tissue engineering [
340
]. More recent examples
include decellularized heart and tracheal tissues [
341
,
342
]. Growth factors and other bioactive
molecules resident in harvested tissue are hypothesized to promote the formation of new matrix.
Reconstituted matrices use this material to form scaffolds that allow for cell seeding and tissue
growth. For example, cartilage tissue can be harvested, homogenized, washed, and then frozen and
lyophilized to create sponge-like scaffolds that promote chondrogenesis in adult stem cells [
343
].
Protein mixtures are another variation on using naturally secreted matrix molecules as scaffold
materials. Matrigel, a commercially available product, has been used extensively as a model basement
membrane for biological experiments [
344
]. Scaffolds formed from materials already present in the
body present an attractive approach to facilitating the natural regeneration process without eliciting
an immune response.
3.3.2 SYNTHETIC SCAFFOLDS
Synthetic scaffold materials are fabricated commercially or in a laboratory, and unlike natural poly-
mers, can be customized in terms of their physical and chemical properties. Specific characteristics
of a polymer, such as its mechanical strength and degradation profile, can be altered through modifi-
cation of its chemical composition. This flexibility allows researchers to design scaffolds with known
degradation rates, biological activity, or specific mechanical characteristics.
Poly-glycolides, poly-lactides, and their copolymers are commonly used for scaffold materials
and other biomedical applications [
345
-
350
]. These polymers can be formed into porous scaffolds,
non-woven meshes, or felts, which allow numerous possibilities for scaffold shape and architec-
ture. Poly-glycolic acid (PGA), perhaps the most commonly used synthetic polymer in cartilage
engineering, is an alpha polyester that degrades by hydrolytic scission. Total degradation can occur
within four to twelve months, which is brief compared to other implanted polyesters [
351
]. Loss of
mechanical properties occurs prior to this, sometimes as early as a few weeks. Since the degradation
products of PGA are naturally resorbed into the body, it is attractive for many medical applications
requiring biocompatibility. PGA can be formed into a porous scaffold by applying a salt-leaching
process. The porosity and interconnectivity of the pores can be controlled by adjusting the amount
of salt included during fabrication. PGA is often extruded as thin strands (
13
μ
m in diameter)
that can be used for making sutures and threads or weaving three-dimensional structures [
352
].
For cartilage engineering purposes, however, PGA is more commonly used in non-woven mesh or
felt forms. The porosity in mesh scaffolds is high, allowing good nutrient transfer throughout the
construct. Furthermore, the interconnectivity of the pores increases seeding efficiency since cells can
infiltrate throughout the scaffold. One major drawback to these mesh scaffolds is their mechanical
functionality. The initial scaffold structure is too weak to be immediately used in loading-bearing
environments. However, growth of neocartilage in the scaffold pores is hypothesized to compen-
sate for the mechanical deficiencies of the scaffold itself. Over time, secreted matrix should fill the
void space, giving the construct sufficient mechanical integrity to withstand the joint environment.
Consistently good extracellular matrix production has been observed using PGA scaffolds, which,
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