Biomimetic Mineralization of Hydrogel Biomaterials for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 55

3.2.3 Hydrogel Composites Based on Synthetic Polymer

Matrices

Although naturally derived hydrogels exhibit benefi cial desirable bio-
logical properties, these materials often display degradation profi les
that are too fast to facilitate hard tissue regeneration. Moreover, chemi-
cal characteristics of natural hydrogels such as the molecular weight are
usually characterized by a wide distribution, which limits the reproduc-
ibility and functionality of the materials. Synthetic hydrogels, on the con-
trary, can be prepared with tailored and highly reproducible chemical
characteristics, thereby allowing for tight control over properties such as
degradability.
The most common synthetic hydrogels that have been studied for
application in bone tissue engineering include hydrogels based either
on poly(ethylene glycol) (PEG), poly(2-hydroxyethyl methacrylate)
(PHEMA) or poly(N-isopropylacrylamide) (PNIPAAm). For instance,
PEG-based hydrogels were used as matrix for the addition of inorganic
nanoparticles by Sarvestani et al. [20], who exploited the calcium-binding
capacity of a glutamic acid peptide sequence (Glu 6 ) to increase the inter-
action strength between inorganic hydroxyapatite nanoparticles and
poly (lactide-ethylene oxide-fumarate) (PLEOF). The peptide was func-
tionalized with acrylate groups that enabled the formation of covalent
bonds between the peptide and the organic polymer. In that way, the
functionalized peptide acted as a linker between inorganic and organic
composite phase. Hydroxyapatite nanocrystals have also been incor-
porated into hydrogels made of oligo(poly(ethylene glycol) fumarate)
(OPF). The introduction of apatitic nanoparticles resulted in a pronounced
increase of acellular calcifi cation in simulated body fl uid (SBF) as well
as mineralized matrix production upon encapsulation of osteoblastic
cells [21-23].
Patel et al. developed cyclic acetal hydrogels reinforced with hydroxy-
apatite nanocrystals for hard tissue engineering [24]. Incorporation of
these nanoparticles into cyclic acetal hydrogels resulted in enhanced
differentiation of bone marrow stromal cells by promotion of endoge-
nous osteogenic signal expression. Elastomeric nanocomposites made of
PHEMA with high mineral contents of about 37-50% were prepared by
Song et al. [25] who exploited the high viscosity of ethylene glycol to facili-
tate dispersion and prevent sedimentation of the hydroxyapatite particles.
The material supported osteoblastic differentiation and bone mineraliza-
tion upon implantation in rats. Gaharwar et al. revealed similar elasto-
meric behavior of photopolymerizable PEG-based hydrogels that contain
hydroxyapatite nanocrystals due to polymer nanoparticle interactions
which interfered with the permanent crosslinking of PEG during pho-
topolymerization [26]. In an alternative approach using self-assembling