Biomimetic Formation of Calcium Phosphate Based Nanomaterials
Doktorsavhandling, 2014

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.

superstructure

lyotropic liquid crystal

self-assembly

Calcium phosphate

bone-like apatite

amphiphilic peptide

nanocomposite

biomimetic mineralization

KB-salen, Kemigården 4, CHALMERS TEKNISKA HÖGSKOLA.
Opponent: Assoc. Prof. Henrik Birkedal, Department of Chemistry, Århus universitet, Danmark.

Författare

Wenxiao He

Chalmers, Kemi- och bioteknik, Teknisk ytkemi

Ur ett materialperspektiv är vårt skelett ett kompositmaterial som består av mineralkristaller, också kallat benapatit, och en proteinmatris som till största delen utgörs av kollagen. Benapatit är sprött medan kollagen är mjukt. Ingen av dem är ensam kapabel att ge både den styrka och seghet som behövs i vårt skelett. En kombination av båda materialen ger däremot utmärkta egenskaper och utgör det kompositmaterial som bygger vårt skelett. Hemligheten bakom de utmärkta bärande egenskaperna hos benen i vårt skelett är den komplimenterande strukturen av hårda och mjuka komponenter vilken har optimerats under miljontals år av evolution. I denna ordnade kollagenstruktur finns spatialt begränsade domäner i vilka apatitkristallerna bildas och växer. Denna process kallas för biomineralisering. Tensider är molekyler med en hydrofil, vattenlöslig del, och en hydrofob, oljelöslig del. Tensider i lösning tenderar att ordna sig på ett sådant vis att den hydrofoba delen av molekylen minimerar sin kontakt med vatten. Vid högre koncentrationer kan högviskösa ordnade strukturer bildas, s.k. vätskekristaller. I denna avhandling har vätskekristaller använts för att skapa syntetiska analoger till de ordnade kollagenmatriserna som återfinns i ben. Tillväxten av apatitkristaller i dessa vätskekristaller har studerats i olika system med syftet att framställa ett kompositmaterial med egenskaper liknande de hos naturligt ben.

From a material perspective, our bone is a composite material consisting of mineral crystallites (called bone apatite) and protein matrix (mainly collagen). These two components are either brittle (mineral) or soft (collagen) and neither of them alone is capable to provide both strength and toughness needed in our skeleton. The secret to the excellent load-bearing properties of bone is the elaborate structure optimized over millions of years of evolution, where the inorganics - apatite platelets are oriented and embedded in the ordered “soft” organics - collagen matrix. In bone, the ordered collagen matrix is organized autonomously and spontaneously (known as the self-assembly process), and then the mineral apatite grows inside the confined water domain in collagen matrix via a process called biomineralization. Surfactant is a group of molecules that could self-assemble in water. This is due to the amphiphilicity of the molecules, meaning a part of the molecule loves water while the other part hates it. This thesis uses such molecules to form liquid crystal phases (gels that are well-ordered) as mimetics to the ordered collagenous structure in bone. The growth of calcium phosphate minerals in different liquid crystal systems was investigated. The long-term aim was to develop artificial bone possessing chemical, structural and mechanical properties in comparable to that of natural bone.

Ämneskategorier

Oorganisk kemi

Materialteknik

Fysikalisk kemi

Biomaterial

Materialkemi

Annan materialteknik

Nanoteknik

Kompositmaterial och -teknik

Styrkeområden

Nanovetenskap och nanoteknik

Materialvetenskap

ISBN

978-91-7597-109-4

Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 3790

KB-salen, Kemigården 4, CHALMERS TEKNISKA HÖGSKOLA.

Opponent: Assoc. Prof. Henrik Birkedal, Department of Chemistry, Århus universitet, Danmark.