Construction of intrafibrillarly mineralized collagen: a review from mechanisms to induction strategies.

Intrafibrillarly mineralized collagen (IMC), the fundamental unit of native bone tissue, is characterized by the inorganic components that crystallize within type I collagen fibrils through tightly regulated biomineralization pathways. It assembles hierarchically to form the complex superstructure and then constitutes the spongy and cortical bone, which endows the bone tissue with superior mechanical properties. With higher matrix stiffness and prolonged ion release, the IMC exhibits enhanced osteogenesis compared to extrafibrillarly mineralized fibrils. Therefore, it is of significant importance to fabricate IMC-based scaffolds in the field of bone tissue engineering (BTE). In this review, the characterization of type I collagen is introduced in the first section, aiming to make the following construction strategies of the IMC easier to understand. Afterward, the hypotheses for the initiation and progression of intrafibrillar mineralization are summarized to provide insights into the advanced fabrication strategy. Finally, the current induction approaches are described to accelerate IMC-based research across laboratories.