Biomimetic Mineralization of Hydrogel Biomaterials for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 52

be implanted using minimally invasive methods since hydrogel compo-
nents can be applied as a liquid that solidifi es in situ . Hydrogels possess
a great versatility regarding the integration of various biomacromol-
ecules and functional groups that can aid in directing tissue regenera-
tion. Furthermore, hydrogels provide a three-dimensional environment
that facilitates controlled biochemical and biomechanical interaction with
encapsulated cells, while their high water content enables diffusion of
nutrients and removal of by-products of cell metabolism and hydrogel
degradation [1, 2]. Hydrogels have been mainly considered for applica-
tions in soft tissue engineering, but the versatility of hydrogels has resulted
in increased interest in potential application of hydrogels in regeneration
of bone and other hard tissues. The inertness - or lack of mineralizing
capacity - of hydrogels, however, is a major drawback that limits their
further use for hard tissue regeneration.
Mineralized, hard tissues in nature are formed via synthesis of an
organic matrix in an aqueous environment that acts as an organic tem-
plate for deposition of an insoluble, dispersed inorganic phase. In bone,
these inorganic components are calcium phosphates (CaPs), which are
fi rst deposited in the form of nanocrystals, which act as nucleation sites
for further crystal growth until the apatitic CaP is the dominant compo-
nent phase. CaPs formation is aided by the presence of calcium-binding
moieties and enzyme-induced increases of the local concentration of free
phosphates.
In this chapter, the following approaches towards mineralization of
hydrogels will be disussed:

- Incorporation of inorganic calcium phosphate (CaP) nanopar-
ticles into hydrogels as seeds for further mineralization
- Incubation of hydrogels in solutions containing calcium
and/or phosphate ions
- Enzymatic mineralization
- Incorporation of mineralization-promoting biomacromolecules

Other approaches, outside the scope of this chapter, include growth
factor and cell encapsulation within hydrogels to promote cell-mediated
mineralization. Readers are referred to reviews on the subject by Salinas
and Anseth [3], Hunt and Grover [4], and Schmidt et al. [5].

3.2 Incorporation of Inorganic Calcium Phosphate

Nanoparticles into Hydrogels

Mineralization of hydrogels by incorporation of apatitic crystals as
seeds for further calcifi cation is the most obvious approach towards