Inorganic ions actively participate in many biological processes, either as essential cofactors to enzymes and proteins or as regulatory molecules in ion channels or secondary signalling. Previous studies focused on the biological performances of individual ions on bone metabolism but overlooked the interactions among ions, and interactions between ions and other components in the localised microenvironment, i.e. cells and organic molecules. In other words, the influence of inorganic components from the bone microenvironment on bone metabolism, and their potential for future biomaterial design for bone tissue engineering remained unexplored.
We developed a low-temperature method for preparing monetite from the bovine femur and generated an ionic environment similar to the bone microenvironment. We found that these inorganic components from the bone microenvironment fostered osteogenesis by upregulating the expression of osteogenesis-related markers (RUNX2, ALP, BMP2, VEGF, OPN), and promoted mineralisation via intracellular mineralisation, without the need for an osteogenic environment. And we further confirmed the great regenerative capacity of inorganic components from the bone microenvironment in vivo. In a rat calvarial defect model, inorganic components from the bone microenvironment-incorporated collagen composite significantly promoted new bone formation in the defect area at 4 and 8 weeks post-operation, verifying the regenerative potential of the inorganic components from the bone microenvironment on in situ bone tissue regeneration in vivo.
Taken together, this is the first study investigating the influence of inorganic components from the bone microenvironment on bone metabolism. We demonstrated the great regenerative capacity of inorganic components from the bone microenvironment on bone tissue engineering. This would bring new insights to future biomaterial design for in situ bone tissue engineering, and provide directions for future studies on a deeper understanding of inorganic components in bone, and other biological processes.