Biomimetic Mineralization of Hydrogel Biomaterials for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 54

The most common natural polymers that have been mixed with calcium
phosphate nanoparticles include collagen (and its denatured derivative
gelatin), fi brin, alginate and chitosan.
Collagen (mostly collagen type I) is the main organic phase of bone tis-
sue and therefore highly biocompatible, enzymatically degradable and pro-
cessable into different forms such as sponges, fi bers, tubes and sheets. An
excellent review was dedicated to the use of collagen as a matrix phase for
the incorporation of calcium phosphate nanocrystals [10]. The incorpora-
tion of hydroxyapatite nanocrystals in gelatin matrices has been studied in
various forms such as sponges, fi lms and microspheres [11-13]. Generally,
the inclusion of hydroxyapatite nanocrystals was shown to reduce degra-
dation and drug release rates whereas the calcifi cation rates increased con-
siderably. Moreover, the osteogenicity of cultured osteoblasts was shown to
be increased by incorporation of hydroxyapatite nanoparticles [11].
Fibrin glue is a synthetic analogue of the blood coagulation process that
creates a fi brin clot upon mixing of fi brinogen and thrombin, and it can
be used as tissue adhesive in a wide variety of surgical applications due
to its favorable biological performance. Le Nihouannen et al. [14] com-
bined these benefi cial properties of fi brin glue in terms of clinical handling
and biocompatibility with the bioactive characteristics of an additional
ceramic phase in order to develop a composite material for bone regen-
eration. Micro- and macroporous biphasic calcium phosphate granules
(hydroxyapatite and b -tricalcium phosphate at a weight ratio of 60/40,
respectively) were mixed with a fi brin glue matrix inducing extensive
mineralization within the fi brin network.
Alginate has the unique capacity to form a gel in the presence of dis-
solved calcium ions, which is a very mild method to create crosslinks in
an organic matrix. Various calcium phosphate phases have been included
in alginate matrices such as gels or beads, either as microstructured
granules or nanosized crystals [15-17]. Crosslinking of alginate matri-
ces can be achieved by addition of soluble calcium sources such as cal-
cium sulphate or calcium chloride. Another method to crosslink alginate
gels involves release of soluble calcium ions from undissolved calcium-
containing precursors such as calcium carbonate or calcium phosphate
by adding acidifi ers such as glucono-delta-lactone (GDL) that induce
partial dissolution of these calcium-containing compounds due to local
acidifi cation [18].
Fedorovich et al. recently compared the effi cacy of osteoinductive
biphasic calcium phosphate microparticles vs. nanosized hydroxyapa-
tite crystals upon embedding in Matrigel hydrogels. Histological and
immunohistochemical analysis of the tissue response revealed that apa-
titic nanoparticles induced osteoclast activation but did not form bone,
whereas biphasic nanoparticles were more effective in inducing ectopic
bone formation [19].