Biomimetic Mineralization of Hydrogel Biomaterials for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 59

ALP has also been applied in fundamental research to test the min-
eralizability of hydrogel materials. Spoerke et al. added ALP to artifi cial
self-assembling peptide amphiphile gels to cause mineralization under
physiological conditions, with the aim of elucidating the role that ALP
itself plays in directing mineral formation [58]. Gungormus et al. used ALP
to compare mineral formation in three different artifi cial self-assembling
peptide hydrogels, showing that ALP can aid in the screening of gels for
mineralizability [59].

3.4.2 Enyzmatic Mineralization for Bone Regeneration

Applications

In the second category, Douglas et al. succeeded in mineralizing mem-
branes of Platelet-Rich Fibrin (PRF), a blood-derived hydrogel material
widely applied in oral and maxillofacial surgery, which led to enhanced
osteoblast spreading [53]. The same group also compared the miner-
alizability of three different hydrogels of interest for bone tissue engi-
neering, namely catechol-poly(ethylene glycol) (cPEG), collagen type
I and OPF [60]. Collagen type I displayed the highest mineralizability
in terms of mineral:polymer ratio after mineralization, while mineral
formation in cPEG was far superior to that in OPF, presumably thanks
to the presence of catechol groups, which are known to have an affi n-
ity for hydroxyapatite [61]. Coatings of polydopamine, which contain
many free catechol groups, were shown by Ryu et al. to be not only
cytocompatible, but also able to promote hydroxyapatite formation on
a wide range of polymeric and metallic biomaterials [62]. Such coat-
ings are formed by substrate immersion in dopamine solution at pH
8.5 [63]. Hydrogels of gellan gum, a polysaccharide crosslinked ioni-
cally by calcium ions, have been used in cartilage tissue engineering
[64]. Functionalization with polydopamine by immersion in dopa-
mine solution led to enhanced mineralization, which in turn promoted
osteoblast adhesion and proliferation [65]. Douglas et al. also incorpo-
rated ALP into thermogelling chitosan/ b -glycerophosphate hydrogels,
which resulted not only in mineralization, but also acceleration of gela-
tion, which is desirable from a clinical point of view [66]. The exact
mechanism by which ALP accelerated gelation is yet to be elucidated.
ALP may split b -glycerophosphate into phosphate ions and glycerol,
which may promote ionic and hydrophobic interactions between chi-
tosan chains, in turn promoting gel formation. Another example of a
system where ALP's action causes gelation was described by Thornton
et al. [67], where dephosphorylation of the hydrogel precursor fl uoren-
9-ylmethoxycarbonyl resulted in reduction of electrostatic repulsion
between monomers, permitting formation of fi brils by hydrophilic and
hydrophobic interactions, which in turn led to gelation.