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THE ROLE OF BIOMOLECULES IN HYDROXYAPATITE BIOMINERALIZATION

Wang, Ziqiu, Wang
http://rave.ohiolink.edu/etdc/view?acc_num=akron1468445118

Abstract Details

, Doctor of Philosophy, University of Akron, Polymer Science.
Bone is a composite material, comprised of collagen protein as the main organic component; hydroxyapatite (HAP) as the inorganic, mineral phase; small molecules such as citrate; and non-collagenous proteins (NCPs). Collagen molecules self-assemble to form fibrils, within which nano-sized, uniquely-shaped, plate-like HAP crystals occur in a specific structural registry. This intra-fibrillar collagen mineralization by plate-like crystal structure provides outstanding biomechanical properties to bone. The various biomolecular components of bone regulate collagen mineralization, but their specific functions are not known. The aim of this study was to explore the potential effects of these biomolecules on bone biomineralization and to identify the corresponding molecular- and nano-level mechanisms. Different stages of bone biomineralization were examined from fibril self-assembly to intrafibrillar nucleation and growth of platy-HAP crystals. In the first part of the study, crystal growth was examined in the presence of small molecules such as amino acids and citrate. Nano-sized, plate-shaped crystals resembling bone mineral were formed. Results of transmission electron microscopy (TEM), solution analysis and molecular dynamic (MD) simulations showed that these small molecules adsorbed preferentially on specific faces of HAP, thus modulating preferred growth directions and, thereby, crystal morphology. This morphology modulation occurs after the collagen fibrils have formed and the mineral has nucleated. In the second part of this study, therefore, we examined the potential roles of a specific NCP, osteocalcin (OCN), in the fibrillogenesis, intrafibrillar nucleation, phase transition and crystal growth. Results of immunoelectron microscopy showed that OCN was associated with the collagen fibrils and affected fibrillogenesis. Intrafibrillar mineralization was achieved in the presence of OCN and an extrafibrillar mineralization inhibitor, fetuin. Similar to bone, platey HAP crystals were formed and aligned parallel to the long axis of collagen. In the absence of either a collagen matrix or fetuin, an amorphous calcium phosphate (ACP) phase was formed and OCN promoted the phase transition to crystalline HAP relative to the control sample. Thus, OCN may influence post-nucleation stages of mineralization such as phase transition or controlling HAP crystal growth or orientation relative to the collagen fibrils. It was in the present study, shown for the first time, that OCN may have multiple functions. Furthermore, synthetic collagen scaffolds mineralized in the presence of OCN showed improved mechanical properties over those mineralized in the absence of OCN. The results of the present study identify and illuminate mechanisms by which NCPs and small molecules may control bone biomineralization and, thus, contribute to the development of treatments for pathological mineralization in various bone diseases. The results also providing design principles for the synthesis of improved biomaterials for bone tissue engineering and other orthopaedic applications.
Nita Sahai (Advisor)
Chemistry

Recommended Citations

Citations

  • Wang, Wang, Z. (n.d.). THE ROLE OF BIOMOLECULES IN HYDROXYAPATITE BIOMINERALIZATION [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1468445118

    APA Style (7th edition)

  • Wang, Wang, Ziqiu. THE ROLE OF BIOMOLECULES IN HYDROXYAPATITE BIOMINERALIZATION. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1468445118.

    MLA Style (8th edition)

  • Wang, Wang, Ziqiu. "THE ROLE OF BIOMOLECULES IN HYDROXYAPATITE BIOMINERALIZATION." Doctoral dissertation, University of Akron. Accessed MAY 01, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=akron1468445118

    Chicago Manual of Style (17th edition)

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© , some rights reserved.Creative Commons License THE ROLE OF BIOMOLECULES IN HYDROXYAPATITE BIOMINERALIZATION by Ziqiu Wang Wang is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Akron and OhioLINK.