Whitlockite: A biomineral from bone to bone repair

Whitlockite (WH), a magnesium-bearing calcium phosphate biomineral, is the second most abundant inorganic component in human bone tissue after hydroxyapatite, and is emerging as a next-generation bone repair material. This review systematically summarizes the research progress of WH in bone tissue engineering, providing a comprehensive overview from fundamental physicochemical properties to cutting-edge biomaterial applications. We first elucidate the unique rhombohedral crystal structure of WH and its functional basis as a reservoir of bioactive ions (Mg²⁺, Zn²⁺, Sr²⁺, etc.), and clarify its regulatory mechanisms in the three key biological processes of osteogenesis, angiogenesis, and neurogenesis. On this basis, we systematically compare the advantages and limitations of three synthesis strategies-precipitation, hydrothermal, and solid-state reactions-in terms of phase purity, crystallinity, scalability, and particle morphology control. Furthermore, we explore four application forms of WH in bone defect repair: bioactive coatings for orthopaedic implants to enhance osseointegration, 3D porous scaffolds that support vascular infiltration, injectable composites that adapt to complex defect geometries, and piezoelectric materials that convert physiological mechanical stimuli into in situ electrical signals to accelerate osteogenesis by leveraging WH's intrinsic piezoelectricity. Finally, we analyze the key challenges in translating WH from laboratory research to clinical practice, and the future directions, including 4D-printed smart scaffolds, ion-coded neuro-vascular-osteogenic coupling, and wireless self-powered piezoelectric regenerative systems. Collectively, these multidimensional attributes of WH offer new insights for the rational design of smart biomaterials that dynamically regulate the regenerative microenvironment and achieve holistic functional bone restoration.