Biomedical Engineering Reference
In-Depth Information
40 CHAPTER 3. IN VITRO TISSUE ENGINEERING
with the mechanical integrity of the construct during early time periods. The resistance of PCL to
rapid hydrolysis is an attractive trait for some applications. Copolymers including PCL incorporate
the strength and elasticity of the material while allowing slightly faster degradation times [ 358 ]. Poly-
L-lactide-epsilon-caprolactone implanted into mice showed formation of cartilage-like structures
after four weeks, with minimal degradation [ 361 ].
A more recent trend for synthetic polymers is to fabricate materials that can control the
attachment of cells and proteins to the scaffold. The most common method to accomplish this
is to modify the hydrophilicity/hydrophobicity of the material. Poly-ethylene glycol (PEG) is a
polymer that prevents adsorption of proteins and cells due to its high hydrophilicity. PEG can be
incorporated into copolymers and thereby modify the cell attachment characteristics of a material.
This property can be used to allow cell attachment on only certain portions of an implant or no
cell attachment at all. The latter is one reason PEG is often used in copolymers - to improve
biocompatibility [ 362 ]. The incorporation of PEG molecules increases hydrophilicity, which helps
to prevent adsorption of antibodies and other proteins, thereby lessening any immune response.
PEG by itself has similar mechanical properties in compression to cartilage, with higher modulus
values corresponding to higher molecular weights [ 363 ]. It has been copolymerized with a number of
different materials to take advantage of its biocompatibility traits to create materials for a variety of
applications [ 317 , 362 , 364 - 370 ]. Copolymerization is also necessary since PEG does not naturally
degrade in the body, an attribute necessary for long-term success of an implanted construct. For
articular cartilage engineering, degradation of the scaffold is necessary to provide space for new
tissue to form.
An alternative approach to synthetic polymers is the creation of macromolecules that imitate
natural biomaterials. Researchers have successfully synthesized genetically engineered molecules,
such as elastin-like polypeptide (ELP), that are similar to natural proteins found in the body [ 371 ].
Chondrocytes cultured in the gelled form of ELP maintained their phenotype, secreting matrix
molecules such as sulfated glycosaminoglycans and collagen.
3.3.3 COMPOSITE SCAFFOLDS
This could include a fiber scaffold formed from several different natural and synthetic threads or a
naturally derived hydrogel infused throughout a synthetic mesh. Composite scaffolds consist of two
or more of the previously discussed materials incorporated into a single scaffold. This could include
a fiber scaffold formed from several different natural and synthetic threads or a naturally derived
hydrogel infused throughout a synthetic mesh. For example, the void fraction of PLGA meshes can
be filled with chondrocytes encapsulated in fibrin glue, which allows for a rounded cell phenotype,
good cell distribution throughout the scaffold, as well as tunable degradation characteristics. This
approach produced 2.6 times more GAG after 4 weeks than PLGA alone [ 372 ]. The inclusion of
fibrin glue might have helped retain GAG molecules in the construct, whereas GAG simply diffused
out of the bare PLGA scaffolds.
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