Biomedical Engineering Reference
In-Depth Information
48 CHAPTER 3.
IN VITRO
TISSUE ENGINEERING
In addition to cell adhesion, extracellular matrix proteins can also promote the haptotactic
and chemotactic motility of chondrocytes. By modifying the adhesion characteristics of a bioma-
terial, cellular migration into a scaffold can be increased or decreased [
422
]. Simple adsorption of
fibronectin onto a polymer scaffold showed an increase in cell attachment and ingrowth compared
to uncoated controls [
423
]. The benefits of increased cell migration have also been observed for
in
vivo
experiments. Hyaluronan scaffolds coated with fibronectin showed increased tissue ingrowth
after implantation into osteochondral defects [
424
]. This ingrowth helped improve integration with
the surrounding bone and cartilage, which is very important for the long-term success of an implant.
One of the more common methods to modify the attachment characteristics of a surface is to
coat it with proteins. The hydrophobicity or hydrophilicity of a material determines the degree of in-
teraction. Hydrophobic materials, in particular, allow proteins to readily adsorb to their surfaces, with
more hydrophobic materials forming a stronger interaction than less hydrophobic materials [
425
].
Following adsorption, cells can then bind to those proteins that coat the bulk scaffold material.
Altering the types of proteins adsorbed to a surface can affect which cells can attach. More generally,
controlling whether proteins can adsorb helps with the biocompatibility of an implant. Some of the
more common adhesion proteins present in the body include collagen, thrombospondin, osteopon-
tin, bone sialoprotein, fibronectin, vitronectin, fibrinogen, von Willebrand factor, laminin, entactin,
and tenascin [
420
,
426
]. Based on the integrin receptors present on chondrocytes, all of the before
mentioned proteins promote adhesion except osteopontin, entactin, and tenascin [
427
]. Typically,
collagen and fibronectin are used for cartilage applications although a wide variety of cell types, not
just chondrocytes, have shown an affinity for these ubiquitous proteins. In native tissues, extracellular
matrix molecules help transmit mechanical and chemical stimuli to cells. Replicating this function
in an engineered construct is one of the hopes associated with protein coating. Naturally secreted
proteins will likely play a more dominant role as the engineered construct develops, but the initial
stages could be assisted by the inclusion of supplementary proteins.
Collagen has been investigated extensively as a bulk scaffold material for tissue engineering
and less so as a protein coating. However, monolayer studies have shown that chondrocytes readily
attach to collagen surfaces [
428
], making it a logical choice as a coating on materials that otherwise
prevent cell attachment. The type of collagen used could play an important role since the primary
collagen in articular cartilage is type II, not type I. Past studies have shown that chondrocytes have
a preference for collagen type II fragments over a type I collagen-coated surface, possibly due to
the integrin receptors expressed by articular chondrocytes [
429
]. While beneficial to cell adhesion,
collagen alone does not appear to retain chondrocyte gene expression when cells are cultured in
monolayer [
97
]. In general, collagen has shown good results as a matrix material, so its use as a
coating has been limited.
Vitronectin is another protein that has been investigated as a scaffold coating for tissue en-
gineering. Past results showed that vitronectin controls osteoblast attachment and spreading, as
opposed to a more ubiquitous protein like fibronectin, when used as a coating
in vitro
[
430
]. This
finding was determined by using culture media without fibronectin or without vitronectin. Samples
