Organized intrafibrillar mineralization, directed by a rationally designed multi-functional protein

Taking lessons from the structure-forming process of biominerals in animals and plants, one can find tremendous inspirations and ideas for developing advanced synthesis techniques, which is called bioprocess inspired synthesis. Bone, as a typical representative of biominerals, is constituted of mineralized collagen fibrils, which are formed under the functions of non-collagenous proteins (NCPs). Intrafibrillar mineralization is the consequence of a synergy among several NCPs. In the present study, we have designed a multi-functional protein, named (MBP)-BSP-HAP, based on bone sialoprotein (BSP) and hydroxyapatite binding protein (HAP), to mimic the intrafibrillar mineralization process in vitro. The three functional domains of (MBP)-BSP-HAP provide the artificial protein with multiple designated functions for intrafibrillar mineralization including binding calcium ions, binding collagen, and binding hydroxyapatite. Platelet-like hydroxyapatite crystals periodically arranged inside the collagen fibrils have been achieved under the function of (MBP)-BSP-HAP. The mechanism of intrafibrillar mineralization directed by the multi-functional protein was proposed. This work may not only shed light on bio-process inspired approaches for more economic and efficient biomimetic synthesis, but also be helpful in understanding the natural process of bone formation for bone regeneration and tissue repair.