Benedini, Luciano A.Moglie, YaninaRuso Beiras, Juan ManuelNardi, SofíaMessina, Paula V.2025-11-202025-11-202021-03-21Cryst. Growth Des. 2021, 21, 4, 2154–2166https://hdl.handle.net/10347/43947This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth & Desing, copyright © 2021 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.cgd.0c01582Numerous 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.engjournal article10.1021/acs.cgd.0c015821528-7505open access