Biomimetic Formation of Calcium Phosphate Based Nanomaterials

Abstract: The intercellular material in bone is a nanocomposite of aligned “hard” inorganics—calcium phosphate (CaP) platelets embedded in the long-range ordered “soft” organic collagen matrix. This elaborate structural arrangement redeems the weaknesses of the individual components (being soft protein or brittle mineral) and gives bone its excellent mechanical properties for the protection and support of our bodies. The structural order and hierarchy in the soft matrix is organized via self-assembly of collagen molecules and is reinforced by intermolecular crosslinking. The subsequent growth of “hard” crystallites inside the “soft” matrix compartments, likely through the deposition of a transient amorphous calcium phosphate (ACP) phase, results in the interpenetrated composite structure. The aim of this thesis was to prepare synthetic mimetics of “hard” material (CaP) with well-defined nanostructures, soft organic matrices with long-range order and interpenetrated composites composing of the two. The work was inspired by the material deposition process in natural bone. Lyotropic liquid crystal (LC) phases self-assembled by block copolymers were used to mimic the structural order of the collagen matrix. Both the inorganic morphogenesis of CaP in LCs and the controlled crystallization of ACP were investigated. To explore ordered organic matrices, crosslinking of the LCs and the self-assembly of an amphiphilic peptide with designed sequence were performed. In addition, controlled mineralization within crosslinked LCs was examined for the formation of nanocomposites. ACP nanospheres, CaP nanowires and nanosheets were prepared from LCs via templated growth. The ACP nanospheres were capable of transforming into bone-like apatite by controlled aging in water and the prepared nanoparticles were shown to affect osteoblast gene expression. Dicalcium phosphate crystals (brushite and monetite) with structural hierarchy and distinct features were also grown in LCs through epitaxial overgrowth or a self-organization regime. Polymerized LCs were successfully prepared from a modified block copolymer (diacrylate derivative of Pluronic® F127), which served as a resilient matrix for the deposition of ACP nanospheres. A subsequent in situ crystallization of ACP into bone-like apatite resulted in mechanically stable composites retaining nanostructures that resembled that of natural bone. An amphiphilic peptide was designed using mainly natural amino acids and it was shown to self-assemble into distinct structures at different concentrations. Based upon the results presented in this thesis, nanomaterials with assorted structures can be further designed for bio-related applications.