Decoupled ionic and particulate clearance pathways determine the in vivo fate of a synthetic nanoclay-BMP-2 biomaterial during ectopic bone induction.

Nanoclay-based biomaterials offer promise for localised growth factor presentation, yet their in vivo degradation, clearance, and systemic fate remain poorly defined. Here, we investigate the fate of a synthetic nanoclay-BMP-2 gel during ectopic bone induction using a combination of in vivo imaging, histology, and component-resolved elemental analysis. Fluorescent tracking confirmed prolonged localisation of BMP-2 within the nanoclay gel and robust bone induction despite negligible growth-factor release. Inductively coupled plasma mass spectrometry (ICP-MS) revealed divergent clearance kinetics for lithium and silicon, structurally distinct components of the clay crystalline lattice, indicating decoupled ionic and particulate degradation pathways. Early clearance was dominated by cell-mediated fragmentation and the transport of clay particulates, while later stages involved preferential lithium release associated with local clay dissolution as well as integration within newly formed bone. Systemic biodistribution analysis demonstrated rapid, transient lithium release into circulation with renal clearance, contrasted with initial hepatic and then later-phase renal handling of silicon species. Together, these findings define a multiphasic in vivo clearance model for nanoclay biomaterials consistent with progressive remodelling, localised BMP-2 activity and, importantly, safe systemic handling. This work provides mechanistic insight into the activity and clearance of nanoclay-based regenerative therapies and establishes the importance of component-resolved tracking for evaluating the biodistribution of degradable inorganic biomaterials.