Biomedical Engineering Reference
In-Depth Information
scaffolds with high porosity and large pore sizes such as meshes and felts [
417
]. Since the degradation
characteristics of the carrier polymer can be customized, protein concentrations are more predictable.
The second method for incorporating growth factors is to bond the bioactive proteins to
the surface of the scaffold material. Covalent bonding is one approach that has been used for
cartilage engineering. The major drawback to this methodology is that immobilizing proteins often
decreases their effectiveness. The active regions of a molecule can be obstructed once bound to a
surface although this is dependent on the protein being bound and the chemical reaction used to
form the covalent bond. Past studies have proven it is possible, though, with one group showing
significant stimulation of cells cultured in a PEG hydrogel that included covalently bound TGF-
β
1 molecules [
418
]. Tethering of growth factors to the scaffold material is a promising means of
retaining activity of the protein while still restricting its movement within a scaffold [
419
]. With
this approach, the growth factor is attached to a molecular chain that extends away from the surface,
allowing greater access while still restricting its diffusion in the construct.
The dramatic stimulation provided by growth factors in cartilage engineering studies suggests
that their inclusion may be required for successful regeneration of the tissue. However, the most
effective means to apply them is still to be determined. Furthermore, the wide variety of growth
factors available creates myriad combinations that could accelerate the growth process, but this
must be tempered by knowledge of what additional effects each growth factor has on the construct
and the surrounding tissues. Cocktails of multiple growth factors might be the best approach to
creating a functional tissue. For example, IGF-1 has been used to increase GAG synthesis, TGF-
β
1 for improving collagen content, and interleukin-4 for minimizing GAG-depleted regions in an
engineered construct [
394
]. Whether growth factors are applied as a soluble mediator, encapsulated
in polymeric carriers, or chemically bound to a scaffold surface, they are an integral part of the
cartilage engineering process and will continue to be a major area of focus for tissue regeneration
therapies in the future.
3.4.2 PROTEINCOATINGAND PEPTIDE INCLUSION
Beside attaching growth factors, scaffold materials can be modified via protein coating, peptide
incorporation, or micropatterning to alter cell attachment characteristics. The first two of these ap-
proaches capitalize on integrin-receptor relationships between cells and extracellular matrix proteins
to direct cell attachment in a controlled manner. Chondrocytes express specific integrins that will
bind with corresponding proteins, so by coating any material with the correct protein, cells can be
made to adhere to almost any bulk structure [
420
]. Integrins identified on chondrocytes include
α
1
β
1
,α
2
β
1
,α
5
β
1
,α
V
β
5
,α
V
β
3
, and
α
3
β
1
, with the latter two being more prevalent on superficial
zone chondrocytes than deep zone chondrocytes [
421
,
422
]. Biomaterials can be modified with
proteins that express one or more of these integrins to control cell attachment to different regions
of the scaffold. While binding between cells and proteins is not permanent, it can at least provide
anchorage points for cells within the construct.
