In vitro models of collagen biomineralization

Abstract

Over the last several years, significant progress has been made toward understanding the mechanisms involved in the mineralization of hard collagenous tissues, such as bone and dentin. Particularly notable are the identification of transient mineral phases that are precursors to carbonated hydroxyapatite, the identification and characterization of non-collagenous proteins that are involved in controlling mineralization, and significant improvements in our understanding of the structure of collagen. These advances not only represent a paradigm shift in the way collagen mineralization is viewed and understood, but have also brought new challenges to light. In this review, we discuss how recent in vitro models have addressed critical questions regarding the role of the non-collagenous proteins in controlling mineralization, the nature of the interactions between amorphous calcium phosphate and collagen during the early stages of mineralization, and the role of collagen in the mineralization process. We discuss the significance of these findings in expanding our understanding of collagen biomineralization, while addressing some of the limitations that are inherent to in vitro systems.

Demineralization–remineralization dynamics in teeth and bone

“…19 Furthermore, mineral exists both within and external to the collagen fibrils (interfibrillar deposition); however, it is generally accepted that the majority of the mineral exists within the fibrils. 30 Interfibrillar mineralization of collagen is directed by the collagen matrix, 31 which leads to nanostructured architecture consisting of uniaxially orientated nanocrystals of HA embedded within and roughly aligned parallel to the long collagen fibril axis. Previous studies have suggested that type I collagen polypeptide stereochemistry and other factors are fundamental in the initial events of mineral deposition with the intrafibrillar spaces of the molecule.…”

“…Tissue localization can give clues to a role but does not provide any functional information. 30 How Ca and PO 4 ions are delivered to the mineralization front is still a matter of debate. Pioneering studies have suggested the role of mitochondria in taking in large amounts of Ca and PO 4 ions, accumulating them, and delivering calcium phosphate in membrane bound vesicles to the extracellular spaces of mineralizing cartilage and bone.…”

Biodegradable mesoporous delivery system for biomineralization precursors

“…17,45 Based on the size exclusion mechanism of intrafibrillar mineralization, 46 PAH is excluded from entering the intrafibrillar compartments of the collagen fibril; depletion of the nucleation inhibitor would result in the formation of crystalline calcium phosphate phases inside the collagen fibril. Because nucleation inhibitors do not need to enter collagen fibrils to induce mineralization, 47 a third theory was recently proposed in which the negatively charged or positively charged polyelectrolytes reside in the extrafibrillar region to establish a balance between electroneutrality and osmotic equilibrium in the vicinity of the collagen fibrils. Establishment of GibbsDonnan equilibrium enables the influx of prenucleation clusters or ACP into the internal milieu of the fibrils to result in intrafibrillar mineralization.…”

Tunability of collagen matrix mechanical properties via multiple modes of mineralization

“…Lines above bars indicate p , 0.05. rsfs.royalsocietypublishing.org Interface Focus 6: 20150070 techniques have been employed. These included simply immersing collagen scaffolds in solutions such as SBF or adding proteins, peptides or other chemicals to help control the mineralization process [3,20,[51][52][53][54][55][56][57]. Simple immersion of collagen leads to surface deposition of mineral either on the surface of fibrils, creating extrafibrillar mineral, or on the surface of dense collagen scaffolds.…”