Regulatory Potency of Oligomeric Proanthocyanidins (<scp>PACs</scp>) on Extrafibrillar and Intrafibrillar Collagen Mineralization

The therapeutic potential of plant-derived proanthocyanidins (PACs) interacting with mammalian collagen is extensive, notably in strengthening specialized extracellular matrix like the dentin matrix, crucial for reparative dental treatments. This study unveils an additional facet of PACs beyond their recognized chemical and biomechanical advantages in fibrillar collagen: specific tannins possess an inherent capability to influence collagen mineralization. By leveraging the degree of polymerization (DP) of PAC oligomers binding directly to type-I collagen, selective control over in vitro mineralization is achieved. Tetrameric PACs (DP=4) exhibit minimal barriers to extrafibrillar mineralization, whereas dimers (DP=2) effectively hinder nucleation/growth of surface minerals, potentially favoring intrafibrillar mineralization pathways. Additionally, our investigation highlights that bound PACs facilitate the infiltration of mineral precursors within collagen fibrils without relying on conventional process-directing agents. These findings underscore the promising utility of oligomeric PACs as a new class of plant-derived process-directing agents (PPDAs) with compelling mineral activities. While our primary focus is exploring mineralization through diverse PAC structures, establishing a translatable collagen mineralization model remains a ultimate goal of this line of research.