Numerous
living structural materials display self-assembly of building
blocks. Biological molecular networks exhibit lyotropic liquid crystalline
properties that can support non-equilibrium pathways influenced by
dynamic processes at the microscale. With the aim of taking a further
step toward the conquest of a biomimetic material to apply in calcified
tissue regeneration, in this work, we have evaluated the chemical
grafting of phosphorous amide (C–N–P) and α-amino
phosphonate (N–C–P) molecular fragments on previously
created biomimetic hydroxyapatite (HA) nanoparticles (nano-HA). Molecular
combinations were selected due to their recognized capability of influencing
bone physiology and pathology. We have assessed the effect of the
type and degree of nano-HA substitution over the spontaneous self-association
of acidic macromolecules that respond to pH stimulation. The produced
materials were inspected by Fourier transform infrared and solid-state
nuclear magnetic resonance spectroscopy, small-angle X-ray scattering,
powder X-ray diffraction, differential scanning calorimetry, thermogravimetric
analysis, and polarized light and high-resolution electron transmission
microscopy. A complete analysis of the experimental data proved that
under specific synthetic conditions, it is possible to obtain substituted-HA
nanoparticles that are able to act as mesogenic agents. These systems
that dynamically respond to pH can be tailored in vitro to induce, at concentration values analogous to biogenic ones, lyotropic
liquid crystal organization on acid macromolecules.