Biomimetic Synthesis of Self-Assembled Mineralized Collagen-Based Composites for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 34

2.3 Biomimetic Synthesis of Self-Assembled

Mineralized Fibrils

2.3.1 In Vitro Self-Assembly of Mineralized Collagen Fibrils

Investigations of the mechanism on the formation and hierarchical assem-
bly of mineralized collagen fi brils are of vital importance for not only
understanding the processes of bone formation during development, but
also offering novel ideas in the design and fabrication of new functional
materials, such as tissue engineering scaffold materials and biomimetic
engineering materials using biomimetic strategies [51]. The most impor-
tant factor in the assembly of mineralized collagen fi brils is the elaborate
alignment of HA crystals and collagen fi brils with proper chemical and
structural interactions. Especially during the initial stage of collagen min-
eralization, how the collagen fi brils regulate HA crystals nucleation and
deposition is still uncertain, although the previous hypothesis that the
collagen/HA alignment is directed by the negatively charged carboxylate
groups on the surface of collagen interacting with calcium ions in HA has
been widely accepted. Direct and solid evidence are therefore quite neces-
sary for confi rming the previous theories.
Many research groups have attempted to mimic the collagen regulated
biomineralization processes in vitro in order to achieve a better under-
standing of the structural organization in naturally occurring calcifi ed tis-
sues. Rhee et al. [52] investigated the nucleation of Ca-P crystals through
chemical interaction with collagen by soaking a collagen membrane in a
supersaturated simulated body fl uid solution. Hartgerink et al. [53] com-
bined the collagen fi brils and calcium phosphate together to obtain a
homogeneously mineralized collagen gel in one process step, consisting
of a three-dimensional network of collagen fi brils covered with calcium
phosphate. Pederson and Ruberti [54] reported a strategy for exploiting
temperature driven self-assembly of collagen and thermally triggered
liposome mineralization to form a mineralized collagen composite.
Cui and colleagues [55] used different compositions of monomeric
collagen and solutions containing calcium and phosphate ions, and then
used either pH or temperature to induce the formation of hierarchically
assembled mineralized collagen fi brils that resembles the structure in
natural bone. The conventional and high-resolution TEM exanimations
revealed the hierarchical organization of the mineralized collagen fi brils
with tiny HA nanocrystals associating specifi cally with the surfaces of the
collagen fi brils, which is the fi rst evidence to support the previous hypoth-
esis (Figure 2.6).
They investigated the nucleation sites and the conformation change of
collagen during the initial stage of collagen mineralization, showing the
interrelationship of collagen molecules and HA crystals. It was found that