A novel osteopontin biomimetic polypeptide induces collagen fiber mineralization in vitro

Collagen fibers reinforced by hydroxyapatite (HA) constitute the fundamental structures of natural bone and dentin, where non-collagenous proteins (NCPs) play a regulatory role in collagen fiber mineralization. However, the precise mechanism underlying this mineralization process remains controversial. Moreover, achieving mineralized materials with high-purity, high-mimetic, and high-efficiency, as well as elucidating the essential state of mineralized precursor, are key issues in making a breakthrough in collagen fiber mineralization. Herein, an osteopontin phosphorylated polypeptide (OPP) was designed to explore the biomimetic mineralization of collagen fibers through mineralized ion stabilization and collagen surface modification. OPP could stabilize calcium and phosphate, forming OPP-prenucleation clusters (OPP-PNCs) with small sizes and long-term stabilization. Additionally, OPP could bind to and modify collagen fibers, thereby reducing the interfacial energy. Compared to Bare-Collagen, OPP-Collagen remarkably enhanced the mineralization efficiency. Molecular dynamics simulations indicated that OPP-Collagen could sequester calcium and phosphate from OPP-PNCs to induce mineralization, while Bare-Collagen lacks this ability. This biomimetic mineralization strategy utilizing OPP-PNCs achieved both intrafibrillar and extrafibrillar mineralization of OPP-collagen fibers. The present study introduces a novel OPP-Collagen mineralization strategy that highlights the regulatory role of NCPs on the surface of natural collagen, offering valuable perspectives into the mechanisms underlying natural mineralization processes.