Biomedical Engineering Reference
In-Depth Information
ing matrices), scaffolds for engineering liver, skin, bone, cartilage, and blood
vessels [149-153], and as coatings for bio-inert implants [154]. For these ap-
plications, collagen is usually processed into various forms such as sponges,
foams, fibers, and gels. The degradation of collagen matrix can be controlled
locally by the cell-secreted metalloproteases such as collagenase [104].
Collagen hydrogels are excellent candidates for musculoskeletal tissue en-
gineering scaffolds because cells can easily adhere onto the gels, and the
scaffold can provide appropriate biological signals to the cells. Both col-
lagen I and collagen II are often employed as a scaffold for cartilage en-
gineering [155-159]. Collagen gels are known to provide a suitable milieu
to chondrocytes so as to retain their phenotype (spherical morphology) in
vitro [159]. In a detailed investigation, Nehrer et al. have compared the
behavior of canine articular chondrocytes in collagen type I and type II
sponges, and their studies showed that type II collagen sponges facilitate
the chondrocyte phenotype, while they de-differentiated into fibroblastic cell
morphology when seeded into collagen type I [155]. A similar observation
regarding the morphology (“fibroblastic” morphology) was observed when
adipose-derived stem cells were seeded into collagen type I scaffold and then
cultured in chondrogenic medium [146]. Interestingly, irrespective of their
morphology, the cells contained within collagen type I scaffold showed higher
biosynthesis compared to scaffolds made out of agarose and alginate as quan-
tified by collagen and GAG synthesis. A similar trend was observed by Qui
et al. where the authors showed a higher proteoglycan synthesis by chondro-
cytes in collagen type II gels [160]. These results indicate the advantage of
having a biologically active scaffold for tissue engineering.
Collagen hydrogels have also been used for bone regeneration. For ex-
ample, Lindsey et al. have shown that the use of collagen gels as a space-filling
agent can facilitate the repair of calvarial defects in a rat model [161]. A com-
posite of Helistat, a crosslinked network of bovine type I collagen, and BMP-2
has been used for osseous regeneration in rabbits with unilateral critical-
sized defects in the radii [162]. Helistat with BMP-2 has shown significant
bone regeneration (comparable to the one treated with autografts) in 8 weeks
time, whereas untreated defects or those treated with Helistat alone showed
hardly any new bone formation.
Although the collagen-based hydrogels have numerous advantages, their
use as tissue-engineering scaffolds is limited due to their inherent phys-
ical weakness. In order to enhance their mechanical properties, chemical
crosslinks are often introduced using various crosslinkers [163] and enzy-
matic reactions [164]. Rault et al. have investigated the effect of various
crosslinkers on the mechanical properties of collagen networks, and found
that they depend strongly upon the crosslinker [165].
Hyaluronic Acid (HA)
: HA, also known as hyaluronan, is composed of
N
-
acetyl-
D
-glucosamine and
D
-glucuronic acid as shown in Fig. 4. It is found
in all mammalian tissues and body fluids, and is highly hygroscopic in na-
