Biomedical Engineering Reference
In-Depth Information
logical conditions, in the presence of a small concentration of certain divalent
cationssuchasCa
2+
,Ba
2+
,andSr
2+
, through the ionic interaction between
the carboxylic group located on the polymer backbone and the cation. The
metal-induced gelation of alginate is attributed to the ability of guluronic
acid chains to form an “egg box”-shaped structure in the presence of alka-
line earth metals [135]. This characteristic feature (cation-induced gelation)
of alginates can be harnessed for minimally invasive applications. However,
such ionically crosslinked alginate hydrogels mainly undergo degradation by
uncontrolled dissolution of polymer chains. Some of these resulting chains
have a high molecular weight and therefore cannot be readily eliminated by
the body. In order to achieve bio-resorbable dissolution products, high mo-
lecular weight alginate chains are broken into smaller segments by treating
them with
-irradiation prior to their gelation [136]. Irradiated alginate hy-
drogels were found to support bone formation in vivo while allowing the
ultimate excretion of the polymer chains by kidneys [30]. In another ap-
proach, partial oxidation of alginate polymer chains has been used to render
them hydrolytically degradable [137]. In addition to metal induced gelation,
alginate hydrogels can also be prepared by crosslinking alginate with other
monomers [104, 138, 139].
Because of their biocompatibility and nontoxic nature, alginate beads have
been used to deliver chondrocytes [140-142], hepatocytes [143], and islets
of langerhans [54] into the body for cell therapy. Alginate has also been pre-
viously used for wound dressing [144] and as a scaffold for musculoskeletal
tissue engineering [30, 145-148]. Chondrocytes are known to de-differentiate
into fibroblast-like cells during their in vitro monolayer expansion, and al-
ginate gels have been used to effectively re-differentiate the de-differentiated
chondrocytes, where the alginate hydrogels provide a three-dimensional en-
vironment to the anchorage independent chondrocytes [140]. The chondro-
cytes that are encapsulated within the alginate hydrogels retain their spherical
cell morphology and produced the cartilage-specific markers: collagen type
II and aggrecan. Despite its advantages, the use of alginate as an ideal scaf-
fold for tissue engineering is limited due to several shortcomings such as
weak mechanical properties, lack of cellular interactions, and uncontrollable
degradation profile. The incorporation of oligopeptides such as arginine-
glycine-aspartic acids (commonly known as RGD peptides) has been utilized
to enhance the adhesive property of alginate to some extent [145-147].
Collagen
: Collagen is the main component of natural ECM and it is found
in many tissues such as bone, tendon, skin, ligament, and other connective tis-
sues. In particular, bone and teeth are made from a collagen-hydroxyapaptite
composite. Collagen is composed of three protein chains wrapped around
each other in a tight triple helix, which entangle with other helices via sec-
ondary interactions to form a thermally reversible hydrogel. The excellent
biological properties of collagen have been used in various applications such
as artificial skin (e.g. collagen is a component of FDA-approved wound dress-
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