Biomimetic Polysaccharides and Derivatives for Cartilage Tissue Regeneration - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 10

Structurally, CS consists of N-acetylglucosamine moiety, similar to
cartilage specifi c ECM component, GAG, which play a critical role in
regulating expression of the chondrocytic phenotype and in support-
ing chondrogenesis both in vitro and in vivo [2-5]. Since GAG properties
include many specifi c interactions with growth factors, receptors and
adhesion proteins, this suggests that the analogous structure in CS may
also have related bioactivities. In fact, CS oligosaccharides have been
shown to have a stimulatory effect on macrophages, and the effect has
been linked to the acetylated residues [15]. Furthermore, both CS and
chitin have been shown to exert chemo-attractive effects on neutrophils
in vitro and in vivo [16, 17].
A number of researchers have examined the tissue response to various
CS-based implants [18-24]. In general, these materials have been found
to evoke a minimal foreign body reaction. In most cases, no major fi brous
encapsulation has been observed. Formation of normal granulation tissue,
often with accelerated angiogenesis, appears to be the typical course of
healing. In the short term (less than 7 day), a signifi cant accumulation of
neutrophils in the vicinity of the implants can be seen, but this dissipates
rapidly and a chronic infl ammatory response does not develop. The stim-
ulatory effects of CS and its fragments on the immune cells mentioned
above may play a role in inducing local cell proliferation, and ultimately
integration of the implanted material with the host tissue.
CS has been investigated as a scaffolding material in cartilage engineer-
ing [37, 38]. Chondrocytes cultured in vitro on CS substrates, maintained
rounded morphology and preserved synthesis of cell-specifi c ECM mol-
ecules [38]. CS scaffolds seeded with chondrocytes showed partial repair
of cartilage defects in vivo . CS was combined with other polymeric materi-
als, like poly(lactic acid), hyaluronan and poly(ethylenimine), to improve
chondrocyte attachment and the consequent cell adhesion, proliferation
and biosynthetic activity [12, 39, 40]. When the human skeletal cells,
derived from predominantly cartilaginous fetal femora, were cultured
within the CS/PEI hydrogels, the cells maintained chondrocyte-like mor-
phology (Figure 1.2e) [12], and the characteristic functional features were
similar to those of normal cartilage.
Composites of CS-alginate-hyaluronan have been evaluated as scaf-
fold for the development of cartilage regeneration, and in vitro experi-
ments showed neocartilage formation, while implanted seeded scaffold
led to partial repair of cartilage defect in vivo [41]. Recently, a thermo-
sensitive CS-pluronic hydrogel has been designed and developed as an
injectable cell delivery carrier for cartilage regeneration. In vitro cell cul-
ture using bovine chondrocytes showed a substantial increase in cell pro-
liferation and GAGs synthesis during an incubation period of 28 days [42].
Furthermore, CS-based scaffolds have also been loaded with growth fac-
tors to promote cartilage regeneration: both CS and collagen/CS/GAGs